It is widely accepted that free-radical-induced oxidative damage is involved with various human diseases, such as cardiovascular diseases, neural disorders, diabetes, obesity, and cancers. Therefore, antioxidants can help in disease prevention by effectively quenching free radicals or inhibiting the damage caused by them. It is recognized that the health effects of natural products, including food and herbal medicines, are generally associated with antioxidative activities or the free-radical-scavenging properties of phytochemicals. This Special Issue (SI) brought together the current research concerning phytochemical antioxidants and critical thinking on the role of antioxidants in reducing oxidative stress in various diseases. The SI provided a platform for biochemists, food scientists, and nutritionists to exchange new ideas. It includes 19 original research papers and 4 reviews, and covered in vitro, in vivo, and human-based studies, such as the antioxidative activities of phytochemicals, molecular mechanisms of phytochemical antioxidants in disease prevention, and the role of phytochemicals or antioxidants in signaling, cell metabolism, and chronic diseases. We would like to thank Prof. Stanley Omaye, the Editor-in-Chief of Antioxidants, for offering us this opportunity to publish "Phytochemical Antioxidants and Health". We appreciate the contributions from authors for their significant findings. We also owe our peer reviewers a huge debt of gratitude for their insightful comments, which helped to improve the quality of the manuscripts published in this SI.